Research group of song wangze, associate professor of Dalian University of Technology: synthesis of all substituted triazoles by transition metal catalyzed cycloaddition reaction

The 1,2,3-triazole compounds synthesized by click chemistry are very important linking modules, which are widely used in the fields of material chemistry, biochemistry and polymer chemistry to connect various functional molecular fragments Although Sharpless and meldal independently developed cuaac to synthesize 1,4-disubstituted triazole compounds, fokin and Jia jointly developed ruaac to synthesize 1, 5-disubstituted triazoles, however, these reactions are limited to the formation of disubstituted triazoles using terminal alkynes as reactants However, all substituted triazole compounds with functional groups at position 4 or 5 are widely found in natural products and drug molecules, which play a unique and completely different physiological role The cycloaddition reaction of azide and internal alkyne is an important method for the direct construction of all substituted 1,2,3-triazole compounds However, the internal alkyne has some disadvantages, such as low activity, poor chemical and regional selectivity Recently, the research group of song wangze, associate professor of Dalian University of technology, has developed two kinds of new transition metal catalyzed "azide internal alkyne" cycloaddition reactions Under mild and water oxygen compatible conditions, a series of 4 or 5 positions have been synthesized with high chemical selectivity and regional selectivity through strategies such as guiding group and controlling reaction sequence All substituted triazole compounds with functional group in the position of No Relevant research results were published in org Lett (DOI: 10.1021 / ACS Orglett 8b02794) About Associate Professor Song wangze, he graduated from Nankai University in 2008, Zhejiang University in 2011, and received his Ph.D from University of Wisconsin Madison from 2011 to 2016 In 2016, he was employed as an associate professor by Dalian University of technology, mainly engaged in the research of transition metal catalyzed cycloaddition reaction and sugar selective synthesis At present, there are 1 doctoral student and 4 master students in the research group The research results have been successively published in international famous journals such as org Lett., adv synth Catalyst., J org Chem., org Bio Chem Frontier research achievements: transition metal catalyzed cycloaddition synthesis of totally substituted triazole compounds through coordination of univalent iridium and amide bond, the regioselectivity of iridium catalyzed "azido endoyne" cycloaddition reaction (iraac) has been completely controlled, and then the author quickly constructs the parent nucleus structure of 5-amido totally substituted triazole compounds The reaction has the advantages of high yield, good regioselectivity, good water oxygen compatibility, etc it can be applied to biorthogonal reactions, and can be well compatible with various biological environments in vivo and in vitro (Fig 1) Figure 1 Application of iraac reaction under biorthogonal conditions (source: org Lett 2017, 19, 6200) through the coordination of monovalent rhodium with sulfur atom, the regioselectivity of rhodium catalyzed "azido thioendoalkyne" cycloaddition reaction (rhaac) has been completely controlled The author further constructed the parent nuclear structure of 5-mercapto or 5-trifluoromethylthio completely substituted triazole compounds (adv synth Catalyst Doi: 10.1002 / ADSC 201801216) Monovalent rhodium has strong π acid, which can activate a variety of internal alkynes to participate in cycloaddition reaction Therefore, the author developed rhodium catalyzed "azido phosphonyl internal alkyne" cycloaddition reaction to synthesize 4-phosphonyl completely substituted triazole compounds (adv synth Catalyst 2018, 360, 2429) This study was selected as the cover article On the basis of rhodium catalyzed "azide thioneiyne" cycloaddition reaction, the author designed a novel oxidation cycloaddition series reaction By adjusting the order of oxidation reaction and cycloaddition reaction, the oxidation state of sulfur atom was changed The oxidation state of sulfur atom has been proved to be able to control the regioselectivity of rhaac reaction, so as to prepare a single 4-sulfonyltotally substituted triazole or 5-sulfonyltotally substituted triazole (Fig 2) Fig 2 Synthesis of total substituted triazoles by rhaac reaction (source: org Lett 2018, 20, 6705) The author found through further study that traditional cuaac reaction and newly developed rhaac reaction can carry out orthogonal reaction due to different reaction activities of terminal and internal alkynes, without mutual influence By using m-CPBA to oxidize the intermediate of thiotriazole for 1s, we can get 5-sulfonyl and 5-sulfinyltriazole compounds for 4S and 5S, but the reaction conditions need to be further optimized to improve the selectivity (Fig 3) Figure 3 Orthogonal reaction of cuaac rhaac (source: org Lett 2018, 20, 6705) conclusion: Song wangze group has developed two kinds of new transition metal catalyzed "azide internal alkyne" cycloaddition reactions Under mild and water oxygen compatible conditions, a series of 4-or 5-position functionalized all substituted triazole compounds have been synthesized with high chemical selectivity and regional selectivity through strategies such as guiding group and controlling reaction sequence The above research work has been supported by the "star sea backbone" cultivation plan of Dalian University of technology, the National Natural Science Foundation and the basic scientific research business fees of the Central University Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.